Neurons convey information electrically and chemically in a highly-organized system. Electrical impulses, known as action potentials (“AP”, hereinafter), traveling along axons converge at presynaptic terminals and are converted into chemical signals, which are neurotransmitters. However, not all the transmitted APs trigger neurotransmitter release at the synaptic junctions, and not all the released neurotransmitters effectively induce postsynaptic APs. Unlike excitatory synapses, at the inhibitory synapses, APs are sequestered for the purpose of orchestration of overall network communication. Therefore, it is essential to distinguish between the excitatory and inhibitory signals in order to understand, mimic, and monitor neural network behavior.
In biological systems, excitatory and inhibitory synapses are determined by synaptic cell adhesion molecules (“CAMs”, hereinafter). Among the interactions between the synaptic CAMs, the trans-synaptic adhesion between postsynaptic neuroligins (“Nlgs”, hereinafter) and presynaptic neurexins (“Nrxs”, hereinafter) is most representative and has been most extensively studied. Scheiffele et al. showed that the Nlgs expressed in non-neuronal cells were sufficient to induce presynaptic differentiation by introduction of presynaptic Nrxs. Furthermore, purified Nlg-1, whose transmembrane domain (TMD) is swapped with glycosylphosphatidylinositol (GPI)-anchoring motif, can successfully induce presynaptic differentiation when docked on glass microbeads that were coated with supported lipid bilayer (SLB) membranes. However, the chemical conjugation of Nlg-1 on polystyrene beads, despite its capability of adhering to Nrx-expressing cells, failed to induce presynaptic differentiation, suggesting that Nlg-1 requires a fluidic lipid bilayer environment for its activity. Additionally, the Nlg-1 is known to form a dimer.